Linked production of antibodies to mammalian DNA and to human polyomavirus large T antigen: Footprints of a common molecular and cellular process?

Objective To test whether the presence of antibodies to human polyomavirus large T antigen, a viral DNA‐binding protein essential for productive polyomavirus replication, correlates with the presence of antibodies to single‐stranded DNA (ssDNA), double‐stranded DNA (dsDNA), or the autologous TATA‐binding protein (TBP). Methods Sera from patients with various diagnosed or suspected autoimmune syndromes were analyzed for the presence of antibodies to T antigen, DNA, or TATA‐binding protein, and correlations were determined. Rheumatoid factor (RF) was studied as a control antibody. Results A highly significant correlation between antibodies to T antigen and antibodies to ssDNA or TATA‐binding protein, but not between anti–T antigen antibodies and RF, was found in all patient groups. Of all sera that were positive for antibodies to dsDNA, 62% were positive for antibodies to T antigen ( P < 0.03). Conclusion A non‐self DNA‐binding protein such as human polyomavirus large T antigen may render DNA immunogenic upon binding to nucleosomes when expressed in vivo. This is indicated by the strong correlation between antibodies to T antigen and antibodies to DNA or TBP and is consistent with a hapten‐carrier model. This model implies cognate antigen–selective interaction of T antigen–specific T helper cells and DNA‐specific B cells or B cells specific for other components of nucleosomes, consistent with the results of previous experiments.